The SenseLab suite of 8 interoperable databases is aimed at supporting our research on a model system for brain organization, the olfactory bulb, and at sharing these and related resources with the neuroscience and neuroinformatics communities. During the past 5 years a Program Project grant has enabled us to begin to move from the synaptic and cell levels to the microcircuit level, and in this R01 grant we will build directly on this work. First, we will continue development of our most heavily used databases - NeuronDB and ModelDB - for the analysis of dendritic signal integration, and ORDB, supporting work on olfactory receptors, the largest family in the genome. We will continue to participate in the Neuroscience Database Gateway, the Neuroscience Information Framework, and the International Neuroinformatics Coordinating Facility. We will continue to demonstrate how databases support neuroscience research with two new research projects to develop computational models that give insight into experimental data. One project is to deepen insight into our recent experimental evidence from transsynaptic tracing for widely distributed cell columns, which we hypothesize are involved in processing odor maps. We will analyze this data and use it to refine first a reduced microcircuit in which the glomerular cell columns respond to the excitatory input from the odor maps and process it through distance-independent lateral inhibition between glomerular columns. With continual testing by the experimental data, we will scale up the model to 100 columns, then to 2,000, to characterize the global processing of odor maps to an extent not possible with experimental methods. This work will be carried out as a pilot project in parallel with the Blue Brain Project in Switzerland on realistically-based large- scale cortical networks. A new database, MicrocircuitDB, will be developed to support this and related studies of microcircuit organization. A second new project will extend our computational analysis of energy demands in the olfactory glomerulus to the lateral inhibitory interactions, to provide a more thorough understanding of the energy demands of the microcircuits that process odor maps. A new database project is to apply NeuronDB and ModelDB to analyzing the impact of the early pathogenesis of neurodegenerative disorders on dendritic signal integration. For this purpose we are developing a new database, Brain Pharmacology (BrainPharm). All of this work will benefit from continued support and development by the Yale Center for Medical Informatics, and by the NEURON simulation environment team. PUBLIC HEALTH RELEVANCE: There is a critical need to understand how signals are processed in nerve cells and nerve circuits as a basis for brain function. We attempt to enhance this effort through a system of interrelated databases of experimental data and computer models. The new projects should give a deeper understanding of both normal brain function and neurological disorders such as Alzheimer's disease